Our aim is to obtain a more precise understanding of the multiple factors possibly related, either singly or in combination, to the pathogenesis of a number of neurological disorders including multiple sclerosis, Sjogrens syndrome, myasthenia gravis, polyneuropathy and other neuromuscular diseases. Focus is currently placed on multiple sclerosis, and studies in this disease consist of a detailed evaluation of the immunological function and immunogenetic background as well as therapeutic trials. Magnetic resonance imaging is being used to assess the extent and magnitude of lesions in the white matter. These studies are performed in patients with sporadic disease, patients with a family history of demyelinating disease as well as identical and nonidentical twins who are either concordant or discordant for the disease. Immunological studies include assessment of cellular immune reactivity to a number of viruses and the analysis of cell surface molecules on leukocytes in the blood and cerebrospinal fluid. Immunoglobulin production and specificity are being evaluated by highly sensitive techniques. Trials of experimental therapeutic approaches are conducted in carefully selected patients with multiple sclerosis. A phase I trial of Poly ICLC, an interferon inducer, has been completed. In another phase I trial blood lymphocytes are transferred from a normal person to an identical twin with multiple sclerosis. A phase III cooperative trial of cyclosporine A in chronic progressive multiple sclerosis is currently in progress. Approximately fifty patients have been randomized into groups that are treated with either cyclosporine A or placebo. During therapeutic trials both the clinical status and immune function are monitored.